Crystals of [S,S]-ethylenediamine-N,N′-disuccinic acid with high bulk density and method of obtaining the same

ABSTRACT

Crystals of [S,S]-ethylenediamine-N,N′-disuccinic acid which have a bulk density of 0.45 to 1.2 g/cm 3 , and a process for obtaining these crystals comprising the steps of adjusting an aqueous solution of an [S,S]-ethylenediamine-N,N′-disuccinic acid metal salt to a temperature of 40 to 80° C. and a pH of 1.9 to 4.5, and cooling the solution to a temperature below 40° C. over a period of 0.2 to 10 hours while supplying a mineral acid so as to maintain the pH at 1.9 to 4.5 to precipitate [S,S]-ethylenediamine-N,N′-disuccinic acid in a high yield.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to [S,S]-ethylenediamine-N,N′-disuccinicacid crystals having a high bulk density and a process for obtaining thecrystals in a high yield. [S,S]-ethylenediamine-N,N′-disuccinic acid(hereinafter abbreviated as [S,S]-EDDS) is expected to find use as abiodegradative chelating agent for a detergent composition, aphotographic bleaching agent, an electroless plating assistant and aperoxide stabilizer, etc.

2. Description of the Background

Several methods are known for a preparation of [S,S]-isomers ofethylenediamine-N,N′-disuccinic acid, such as (1) a chemical syntheticmethod in which said isomers are synthesized from L-aspartic acid anddibromoethane in a basic aqueous medium according to Neal and Rose etal. (Inorganic Chemistry, Vol. 7, pp. 2405-2412, 1968), (2) a chemicalsynthetic method in which the isomers are synthesized from L-asparticacid and dibromoethane in the presence of calcium hydroxide according toPatel R. N. et al. (WO95-12570), (3) an enzymatic synthetic method inwhich the isomers are synthesized from fumaric acid and ethylenediamineaccording to Endo et al., and (4) a fermentative methods usingactinomyces according to T. Nishikiori et al. (J. Antibiot. 37, 426-427,1994) and Z. Hans et al. (WO9636725).

As methods for recovering [S,S]-EDDS, there have been proposed, forexample, a method in which an [S,S]-EDDS solution is gradually madeacidic with a concentrated hydrochloric acid till reaching the pH of 3.5and then an objective substance is recovered from the solution accordingto Neal and Rose et al., a method for recovering from a clacium salt of[S,S]-EDDS (WO96-01801) according to Atkinson. Eldon. E. et al., and amethod for recovering from an aqueous solution of [S,S]-EDDS andL-aspartic acid salt according to Atkinson. Eldon. E. et al.(WO96-01802). These proposals relate to techniques for recovering[S,S]-EDDS from an [S,S]-EDDS solution obtained by a chemical synthesisfrom L-aspartic acid and dibromoethane, and these techniques areintended to minimize an uptake of coprecipitates at the time of arecovery and to obtain a precipitate in such an amount that theprecipitate can be easily filtered. Any of these proposals, however, aresilent on how to obtain the crystals of [S,S]-EDDS with a high bulkdensity in a high yield.

According to experiments by the present inventors, the ordinaryacid-precipitation method for example which comprises adding a mineralacid at a normal temperature or under cooling to a reaction liquid of[S,S]-EDDS obtained by the enzymatic synthetic method (3) as mentionedabove involved problems that precipitated [S,S]-EDDS was extremely highbulky needle crystals, a deterging efficiency was bad, a dryingefficiency of the produced crystals was bad, and a transportationefficiency of the crystals was poor because of their large volume perunit weight.

In order to solve the above problems, the present inventors have madeextensive studies on crystallization conditions of [S,S]-EDDS such as atemperature, pH and a period of time at the time of the crystallization.In result, the present inventors found out the conditions under whichcolumnar crystals having a high bulk density can be obtained, and quiteunexpectedly confirmed that a considerable amount of cyclized productsof ethylenediamine-N,N′-disuccinic acid represented by the followingstructural formulae (1) and (2) etc. were contained in a mother liquorin which formed crystals were removed, and that certain crystallizationconditions promote an intramolecular cyclization reaction to cause areduction of a recovery yield of [S,S]-EDDS.

SUMMARY OF THE INVENTION

Accordingly, the purpose of the present invention is to suppress aformation of the cyclized products of [S,S]-EDDS at the time ofcrystallization and simultaneously to solve the various problemsencountered in obtaining the [S,S]-EDDS crystals having a high bulkdensity. Solution of these problems is of vital importance for theindustrial production of the crystals of [S,S]-EDDS.

Regarding cyclized products of ethylenediamine-N,N′-disuccinic acid,those derived from isomeric mixtures thereof ([R,R]-, [S,S]- and[R,S/S,R]-mixtures) have been reported by Vasil'ev V. P. et al. (Zh.Neorg. Khim. 34(2), 381-385, 1989) and other researchers. However, therehas been report neither on cyclized products derived from opticallyactive [S,S]-isomers alone nor on a formation of the cyclized productsat the time of crystallization.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As a result of intensive studies for a solution of the above problems,the present inventors found that it was effective for solving the aboveproblems to conduct a crystallization under specified pH, temperatureand period of time conditions, and succeeded in completing the presentinvention on the basis of this finding.

Thus, the present invention relates to: (1) crystals of[S,S]-ethylenediamine-N,N′-disuccinic acid having a bulk density of from0.45 to 1.2 g/cm³; (2) a process for obtaining the crystals described in(1), which comprises the steps of adjusting an aqueous solution of an[S,S]-ethylenediamine-N,N′-disuccinic acid metal salt to a temperatureof from 40 to 80° C. and a pH of from 1.9 to 4.5 and then cooling theresulting solution to a temperature below 40° C. over a period of from0.2 to 10 hours while supplying a mineral acid thereto so as to maintainthe pH at from 1.9 to 4.5 to precipitate[S,S]-ethylenediamine-N,N′-disuccinic acid in a high yield; (3) theprocess for obtaining the crystals described in (1), which comprises thesteps of supplying an aqueous solution of an[S,S]-ethylenediamine-N,N′-disuccinic acid metal salt and a mineral acidinto an aqueous solution of an [S,S]-ethylenediamine-N,N′-disuccinicacid metal salt adjusted to a temperature of from 0 to 40° C. and a pHof from 1.9 to 4.5 so as to maintain the pH at from 1.9 to 4.5 and so asto make a residence time from 0.5 to 10 hours, and taking outintermittently or continuously the resulting slurry of[S,S]-ethylenediame-N,N′-disuccinic acid crystals in a high yield; (4)the process described in (2) or (3), wherein the yield of the crystal is90% or more; (5) the process described in (4), in which a cyclization of[S,S]-ethylenediamine-N,N′-disuccinic acid during its crystallization issuppressed; (6) the process described in (2) or (3), wherein the[S,S]-ethylenediamine-N,N′-disuccinic acid metal salt is a sodium saltand/or a magnesium salt; and (7) the process described in (2) or (3),wherein the mineral acid is a sulfuric acid.

[S,S]-EDDS contemplated in the present invention is the one having acomposition that a ratio of [S,S]-isomers to a whole amount of isomersis 90% by weight or more.

The term “bulk density” referred to in the present invention is definedas a value determined according to JIS K5101 for a dry product with awater content (including crystal water) of 15% by weight or less.

The term “yield” referred to in the present invention is a valuedetermined by dividing a weight obtained by subtracting a weight of[S,S]-ethylenediamine-N,N′-disuccinic acid disappearing at the time ofcrystallization from a weight of [S,S]-ethylenediamine-N,N′-disuccinicacid present in an aqueous solution of anethylenediamine-N,N′-disuccinic acid salt, by a weight of[S,S]-ethylenediamine-N,N′-disuccinic acid present in the originalaqueous solution, said value being expressed by percent.

Crystallization can be accomplished, for example, in the following way.In the case of a batch process, an aqueous solution of an alkaline metalsalt, alkaline earth metal salt or ammonium salt etc. of [S,S]-EDDS witha concentration of from 0.1% by weight to a saturation concentration,obtained by the above-mentioned enzymatic synthetic method from fumaricacid and ethylenediamine (JP-A-9-140390 and EP-A-0805211), is adjustedto a pH in the range of 1.9 to 4.5, preferably 2.5 to 4.0, and atemperature in the range of 40 to 80° C., preferably 40 to 60° C., and,if necessary after causing a partial precipitation of [S,S]-EDDS orafter adding seed crystals of [S,S]-EDDS, is gradually cooled. Coolingtemperature is below 40° C., preferably 30 to 0° C., and cooling time,although variable depending on pH and temperature conditions, is in therange of from 0.2 to 10 hours. In the case of a continuous process,after adjusting the pH to the range of 1.9 to 4.5, preferably 2.4 to4.0, and the temperature to the range of 0 to 40° C., an aqueoussolution of an alkaline metal salt, alkaline earth metal salt orammonium salt etc. of [S,S]-EDDS is supplied thereto so that a residencetime become 0.5 to 10 hours, preferably 1 to 5 hours, although variabledepending on pH and temperature conditions, and the resulting [S,S]-EDDScrystal slurry is taken out continuously or intermittently.

Although pH rises up gradually with proceeding of a crystallization, pHis adjusted so as to be in a prescribed range by adding an acid asrequired in this case.

Such pH adjustment can be usually made by adding a mineral acid such assulfuric acid or hydrochloric acid.

On the other hand, the lower the pH or the higher the temperature or thelonger the period of time of an exposure to these conditions, the easierformation of the cyclized products of ethylenediamine-N,N′-disuccinicacid represented by the structural formulae (1) and (2). The formationof the cyclized product not only causes a reduction of a recovery yieldof the [S,S]-EDDS crystals but results in a cause of a reduction of acrystal quality because the cyclized product remaining in a motherliquor adheres to the crystals. However, the use of the above-mentionedpreferable conditions can control a less formation of the cyclizedproduct. According to the present invention, it is possible to finallyobtain the [S,S]-EDDS crystals in a yield of 90% or more.

Ordinary methods such as filtration, centrifugation, etc., can beemployed for collecting the the precipitated crystals. Then, thecyclized product and sulfates etc. formed in the acid-precipitation ofcrude crystals are washed away with water or an organic solvent. Thiswashing is not subject to any specific restrictions, either, andordinary washing methods such as rinsing and slurry washing etc. can beemployed.

Drying of wet crystals after washing may be conducted at such atemperature that a temperature of the product be 80° C. or less.

The present invention is further illustrated by the following examples,but it should be understood that the present invention is not restrictedby these examples in any way.

Methods of analyses and measurements made in the following Examples areas described below.

(1) [S,S]-EDDS and its Cyclized Product

An [S,S]-EDDS solution or a 0.5N sodium hydroxide solution of crystalsthereof centrifugally sterilized were analyzed by liquid chromatography(column: Inertsil ODS-3; mobile phase: 2 mM tetra-n-butylammoniumhydroxide, 2 mM CUSO₄ and 50 mM H₃PO₄; flow rate: 1.0 ml/min;temperature: 40° C.; detecting wavelength: 220 nm).

(2) Optical Purity of Ethylenediamine-N,N′-disuccinic Acid

An [S,S]-EDDS solution or a 0.5N sodium hydroxide solution of crystalsthereof, in which cells had been centrifugally removed, were analyzed byliquid chromatography (column: MCl GEL CRS 10W; mobile phase: 10 mMCuSO₄; flow rate: 0.5 ml/min; temperature: room temperature; detectingwavelength: 254 nm).

(3) Bulk Density

Bulk density of dry crystals obtained was measured by a bulk densitymeasuring instrument mfd. by Tokyo Kuramochi Kagaku Kikai SeisakushoLtd. (JIS K5101).

Production Example 1

Preparation of [S,S]-EDDS Solution

Brevundimonas sp. TN-3 strain was cultured to obtain strain cellsaccording to the method described in Example 1 of JP-A-9-140390. ThisTN-3 strain is described in EP-A-0805211, and it was deposited withNational Institute of Bioscience and Human Technology, Agency ofIndustrial Science and Technology (1-3, Higashi 1-chome, Tsukuba-shi,Ibaraki-ken, Japan) on Apr. 11, 1996, and was afforded InternationalDeposit No. FERM BP-5886 according to Budapest Treaty on theInternational Recognition of the Deposit of Microorganisms for thePurpose of Patent Procedure. The strain cells were suspended in a 100 mMboric acid buffer of pH 9.2 and heat-treated at 45° C. for 8 hours.

The treated strain cells were collected and then were suspended in a pH8.5 reacting solution containing 143 g/l of fumaric acid, 37 g/l ofethylenediamine and 54 g/l of magnesium hydroxide and reacted withstirring at 40° C. for 3 days while adjusting pH of the reaction mixtureat 8.5 with a sodium hydroxide solution.

After the reaction was completed, the reaction product solution wascentrifuged for removing the cells. The obtained supernatant contained480 mM [S,S]-EDDS (a ratio of [S,S]-form to whole isomers being 98.8% byweight) and completely free of cyclized product of [S,S]-EDDS.

Comparative Example 1

Sulfuric acid was added to 100 ml of the above [S,S]-EDDS solution atroom temperature (20° C.) to adjust its pH at 1.95. The solution wasallowed to stand for one hour and precipitated crystals were filtered bya Buchner funnel and washed with 100 ml of desalted water to obtain wetcrystals. Drying thereof overnight at 80° C. gave needle crystals(0.05-0.2 mm in diameter and 0.5-3 mm length) with a bulk density of 0.2g/cm³ in a yield of 99.5%. Sulfate in the crystals was 264 ppm, and anamount of cyclized product in a mother liquor was about 0.5% based on[S,S]-EDDS supplied.

Comparative Example 2

To 100 ml of the above [S,S]-EDDS solution heated to 90° C., sulfuricacid was added to adjust its pH at 3.0. Then the solution was cooledgradually over a period of 2 hours until reaching 30° C., during whichperiod sulfuric acid was gradually added to maintain pH at 3.0.Precipitated crystals were. filtered by a Buchner funnel and washed with100 ml of desalted water to obtain wet crystals. Drying thereofovernight at 80° C. gave columnar crystals (0.3-0.6 mm in diameter and1-3 mm length) with a bulk density of 0.6 g/cm³ in a yield of 80%. Anamount of cyclized product in a mother liquor was about 20% based on[S,S]-EDDS supplied.

Comparative Example 3

To 100 ml of the above [S,S]-EDDS solution heated to 40° C., sulfuricacid was added to adjust the pH at 3.0, to which the above [S,S]-EDDSsolution was further supplied at a rate of 1,000 ml/hr. In thisoperation, a slurry was taken out from time to time so as to maintain aliquid level at 100 ml (residence time: 0.1 hour). Also, during thisperiod, sulfuric acid was gradually added to maintain the pH at 3.0.Precipitated crystals were filtered by a Buchner funnel and washed with100 ml of desalted water to obtain wet crystals. Drying thereofovernight at 80° C. gave columnar crystals (0.1-0.2 mm in diameter and0.3-1 mm length) with a bulk density of 0.3 g/cm³ in a yield of 99.5%.

EXAMPLE 1

To 100 ml of the above [S,S]-EDDS solution heated to 80° C., sulfuricacid was added to adjust pH at 3.75. Then the solution was cooledgradually over a period of 2 hours until reaching 30° C., during whichperiod sulfuric acid was gradually added so as to maintain pH at 3.75.Precipitated crystals were filtered by a Buchner funnel and washed with100 ml of desalted water to obtain wet crystals. Drying thereofovernight at 80° C. gave columnar crystals (0.3-0.6 mm in diameter and1-3 mm length) with a bulk density of 0.58 g/cm³ in a yield of 91.5%.Sulfate in the crystals was 97 ppm, and an amount of cyclized product ina mother liquor was about 8.5% based on [S,S]-EDDS supplied.

EXAMPLE 2

To 100 ml of the above [S,S]-EDDS solution heated to 80° C., sulfuricacid was added to adjust pH at 3.2. Then, the solution was cooled to 60°C. over a period of 30 minutes, maintained at 60° C. for one hour andthen again cooled gradually till reaching 21.5° C. over a period of onehour. During this period, sulfuric acid was gradually added to maintainthe pH at 3.2. Precipitated crystals were filtered by a Buchner funneland washed with 100 ml of desalted water to obtain wet crystals. Dryingthereof overnight at 80° C. gave columnar crystals (0.3-0.6 mm indiameter and 1-3 mm length) with a bulk density of 0.57 g/cm³ in a yieldof 95.0%. Sulfate content in the crystals was 94 ppm, and an amount ofcyclized product in a mother liquor was about 5% based on [S,S]-EDDSsupplied.

EXAMPLE 3

To 100 ml of the above [S,S]-EDDS solution heated to 60° C., sulfuricacid was added to adjust pH at 3.2. The solution was maintained at 60°C. for 30 minutes and then cooled gradually until reaching 21.5° C. overa period of one hour. During this period, sulfuric acid was graduallyadded to maintain the pH at 3.2. Precipitated crystals were filtered bya Buchner funnel and was washed with 100 ml of desalted water to obtainwet crystals. Drying thereof overnight at 80° C. gave columnar crystals(0.3-0.6 mm in diameter and 1-3 mm length) with a bulk density of 0.55g/cm³ in a yield of 98.0%. Sulfate content in the crystals was 93 ppm,and an amount of cyclized product in a mother liquor was about 3% basedon [S,S]-EDDS supplied.

EXAMPLE 4

To 100 ml of the above [S,S]-EDDS solution diluted to 3 times and heatedto 40° C., sulfuric acid was added to adjust pH at 3.2. Then, thesolution was maintained at 60° C. for 30 minutes and then cooledgradually till reaching 20° C. over a period of one hour. During thisperiod, sulfuric acid was gradually added to maintain the pH at 3.2.Precipitated crystals were filtered by a Buchner funnel and washed with100 ml of desalted water to obtain wet crystals. Drying thereofovernight at 80° C. gave columnar crystals (0.2-0.7 mm in diameter and1-3.5 mm length) with a bulk density of 0.56 g/cm³ in a yield of 99.5%.Sulfate content in the crystals was 90 ppm, and an amount of cyclizedproduct in a mother liquor was about 0.5% based on [S,S]-EDDS supplied.

EXAMPLE 5

To 100 ml of the above [S,S]-EDDS solution heated to 40° C., sulfuricacid was added to adjust pH at 3.0, to which the above [S,S]-EDDSsolution was further supplied at a rate of 50 ml/hr. In this operation,a slurry was taken out from time to time so as to keep a liquid level at100 ml (residence time: 2 hours). During this period, sulfuric acid wasgradually added to maintain the pH at 3.0. Precipitated crystals werefiltered by a Buchner funnel and washed with 100 ml of desalted water toobtain wet crystals. Drying thereof overnight at 80° C. gave columnarcrystals (0.3-0.7 mm in diameter and 0.5-1 mm length) with a bulkdensity of 0.61 g/cm³ in a yield of 99%.

EXAMPLE 6

To 100 ml of the above [S,S]-EDDS solution heated to 20° C., sulfuricacid was added to adjust pH at 3.0, to which the above [S,S]-EDDSsolution was further supplied at a rate of 30 ml/hr. In this operation,a slurry was taken out from time to time so as to keep a liquid level at100 ml (residence time: 3.3 hours). During this period, sulfuric acidwas gradually added to maintain the pH at 3.0. Precipitated crystalswere filtered by a Buchner funnel and washed with 100 ml of desaltedwater to obtain wet crystals. Drying thereof overnight at 80° C. gavecolumnar crystals (0.3-0.6 mm in diameter and 0.4-1 mm length) with abulk density of 0.58 g/cm³ in a yield of 99.5%.

Industrial Applicability

Crystals of [S,S]-EDDS according to the present invention are columnarcrystals (about 0.3-0.7 mm in diameter and about 0.5-1 mm length) with abulk density of 0.45 to 1.2 g/cm³. These crystals are far better inwashing, drying and transporting efficiencies than needle crystals(about 0.05-0.2 mm in diameter and about 0.5-3 mm length) with a bulkdensity of about 0.2 g/cm³ obtained by the conventionalacid-precipitation method in which a mineral acid is added at normaltemperature or under cooling. Also, the [S,S]-EDDS crystals of thepresent invention are substantially free of impurities such as salts andcyclized product of [S,S]-EDDS formed during acid precipitation, henceare high in quality. Further, these crystals can be obtained in a highyield.

What is claimed is:
 1. A process for producing crystals of(S,S)-ethylenediamine N,N′-disuccinic acid, which are columnar having abulk density of from 0.45 to 1.2 g/cm³, comprising the steps ofadjusting an aqueous solution of an (S,S)-ethylenediamine-N,N-disuccinicacid metal salt to a temperature of 40 to 80° C. and a pH of from 2.5 to4.0, partly precipitating or adding crystals of(S,S)-ethylenediamine-N,N-disuccinic acid, and then cooling theresulting solution to a temperature below 40° C. over a period of from0.2 to 10 hours while supplying a mineral acid thereto so as to maintainthe pH range to precipitate (S,S)-ethylenediamine-N,N-disuccinic acid ina yield of 90% or more.
 2. A process for producing crystals of(S,S)-ethylenediamine-N,N′-disuccinic acid, which are columnar crystalshaving a bulk density of from 0.45 to 1.2 g/cm³, comprising the steps ofsupplying an aqueous solution of an(S,S)-ethylenediamine-N,N′-disuccinic acid metal salt and a mineral acidinto an aqueous solution of an (S,S)-ethylenediamine-N,N′-disuccinicacid metal salt adjusted to a temperature of from 0 to 40° C. and a pHof from 2.5 to 4.0 so as to maintain the pH range and so as to make aresidence time from 0.5 to 10 hours, and taking out intermittently orcontinuously the resulting slurry of(S,S)-ethylenediamine-N,N,′-disuccinic acid crystals in a yield of 90%or more.
 3. The process of claim 1, in which cyclization of(S,S)-ethylenediamine-N,N′-disuccinic acid during crystallization issuppressed.
 4. The process of claim 1, wherein the(S,S)-ethylenediamine-N,N′-disuccinic acid metal salt is a sodium saltor a magnesium salt.
 5. The process of claim 1, wherein the mineral acidis sulfuric acid.
 6. The process of claim 2, in which cyclization of(S,S)-ethylenediamine-N,N′-disuccinic acid during crystallization issuppressed.
 7. The process of claim 1, wherein said aqueous solution ofan (S,S)-ethylenediamine-N,N′-disuccinic acid metal salt is adjusted toa temperature of from 40 to 60° C.
 8. The process of claim 1, whereinsaid aqueous solution of an (S,S)-ethylenediamine-N,N′-disuccinic acidmetal salt is cooled to a temperature of from 0 to 30° C.
 9. The processof claim 1, having a yield of from 91.5 to 99.5%.
 10. The process ofclaim 1, wherein the columnar crystals produced are about 0.3-0.7 mm indiameter and about 0.5-1 mm in length.
 11. The process of claim 2,wherein the columnar crystals produced are about 0.3-0.7 mm in diameterand about 0.5-1 mm in length.
 12. The process of claim 1, wherein thecolumnar crystals produced have a bulk density of from 0.55 to 0.61g/cm³.
 13. The process of claim 2, wherein the columnar crystalsproduced have a bulk density of from 0.55 to 0.61 g/cm³.